Interactions between connective tissue cells and their environment, finely regulated in the course of normal growth and remodelling, are distorted in several skeletal disorders. Pathophysiologic mechanisms underlying cartilage degradation and repair will be studied in two prevalent articular diseases - rheaumatoid and osteoarthritis. Cartilage - synovial interactions will be examined in a model organ co-culture system using cartilage discs and samples of diseased synovium from human rheumatoid or experimental animal arthritides. Proteoglycan release will serve as a quantitative measure of matrix depletion, and breakdown products will be characterized by chromatographic techniques. The biosynthetic response of proteoglycan and collagen during repair will be assessed by radioactive labelling and chemical isolation methods. The system should prove useful in evaluating therapeutic agents. Chondrocyte-matrix interactions will be examined in cell culture. Chondroid expression will be assessed in terms of proteoglycan and collagen biosynthetic patterns in several culture conditions. Differences in cartilage phenotype depending on cellular microenvironment will be examined in rabbit articular chondrocyte monlayaer and spinner cultures as a function of age. The role of cellular senescence in the loss of chondroid expression will be examined in progressively aged cells by clonal culture methods. Rat costal growth cartilage chondrocytes which are of high osteogenic potential and retain their hormonal responsiveness, will be studied as a model differentiating system.